The invention deals with an agent, able to affect the hyperactivated immununological effector cells and with its use.
Different situations and disorders of humans are associated with a hyperactivated state of the immunological effector cells, caused e.g. by cytokines; such effector cells lose their ability to respond to new specific signals. The immune system is impaired or even switched off in such situations. This occurs e.g. following a persistent stimulation during a prolonged infection or in situations of cell hyperactivation due to an excessive release of endogenous cytokines. The term "immunological effector cells" comprises e.g. T cells, macrophages/monocytes, NK cells and other immunological cells.
A variety of immunological processes include on the cellular level the cyclic adenosine phosphate (cAMP) which is produced by the enzyme adenylate cyclase (AC) from adenosine triphosphate (ATP). The cAMP plays as "second messenger" a central role in the hormonal regulation as well as in the metabolism (through activation of protein kineses, e.g. protein kinase A (PKA). The PKA phosphorylates proteins which in turn depress the immune response. In this way, the hyperactivation of effector cells results in the down regulation of the immune function.
This reaction cascade is regulated by the production of cyclic guanosine monophosphate (cGMP) which antagonizes the cAMP. This reaction cascade is also influenced by the group of G-protein coupled receptors, comprising receptors such as adrenergic, muscarinic, histamine, serotonin and adenosine receptors. The G-proteins (guanine nucleotide-binding proteins) are able to stimulate (Gs) or to inhibit (Gi) the production of second messengers. By affecting either the Gs- or the Gi-receptors, the stimulation of AC and herewith the cAMP-production can be regulated. Situations with a disturbed equilibrium are e.g. cancer, viral diseases and autoimmune disorders, as well as the inducing and disease-maintaining component of the atherosclerosis.